Can medicines development improve outcomes in asthma and chronic obstructive pulmonary disease management by driving effectiveness?

Abstract

Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients. The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals. Here we discuss the concept of “drivers of effectiveness”— features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors — and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials. Using the Salford Lung Studies (SLS) in asthma and COPD as an illustrative example, we discuss various features of the inhaled corticosteroid/long-acting β 2 -agonist combination, fluticasone furoate/vilanterol (FF/VI), as potential drivers of effectiveness that may have contributed to the improved patient outcomes observed with initiation of FF/VI versus continuation of usual care in the UK primary care setting.

Effectiveness of individualized inhaler technique training on low adherence (LowAd) in ambulatory patients with COPD and asthma

“…However, logistical limitations conditioned the design to a pre-post intervention study, thus incorporating possible biases to the results obtained. Occasionally, studies with minimal exclusion criteria may be more representative of the patients seen in daily clinical practice and provide complementary data to those obtained in traditional efficacy studies 39 .…”

24-Hour Serial Spirometric Assessment of Once-Daily Fluticasone Furoate/Umeclidinium/Vilanterol Versus Twice-Daily Budesonide/Formoterol in Patients with COPD: Analysis of the FULFIL Study

“…This is further supported by the greater proportion of patients achieving a clinically meaningful increase of ≥ 100 mL in FEV 1 during the first 6 h after administration of FF/UMEC/VI on day 1 compared with twice-daily BUD/FOR (90% vs 76%) and the shorter median time to achieve this increase (30 vs 39 min). The rapid onset of a medication has been suggested as a potential encouragement for patients adhering to their treatment [ 13 , 14 ], while a longer duration of action may provide greater tolerance for patients not adhering to their treatment schedule [ 14 ]. As adherence is not only related to the dosage of medication but also the timing of the administration [ 15 ], simplifying treatment regimens from a twice-daily to once-daily regimen may improve adherence and potentially clinical outcomes [ 16 – 18 ].…”

Measuring and reporting treatment adherence: What can we learn by comparing two respiratory conditions?

“…61 Given that drug effects may persist for several days after administration, 62 asthma medications with longer durations of efficacy may be particularly forgiving. [63][64][65] Importantly, the same medication may also be eliminated at different rates in different people (known as "pharmacokinetic variability"), based on factors such as age, sex, smoking status and body size. 66-68…”

“…Recent evidence indicates that asthma is forgiving to poor therapy adherence, and that it is possible to achieve similar levels of exacerbation reduction in mild asthma with less frequent doses of inhaled steroids than are typically prescribed 61 . Given that drug effects may persist for several days after administration, 62 asthma medications with longer durations of efficacy may be particularly forgiving 63–65 . Importantly, the same medication may also be eliminated at different rates in different people (known as “pharmacokinetic variability”), based on factors such as age, sex, smoking status and body size 66–68 …”